The overall aims of this renewal application are to prove that magnetic resonance imaging and magnetic resonance spectroscopy (MRI/MRS) measurements can predict development of Alzheimer's Disease (AD), and that serial MRI/MRS measurements are valid biomarkers of AD disease progression. We will study three clearly distinguishable clinical groups: 1) cognitively normal elderly subjects, 2) patients with probable AD and 3) patients with a mild cognitive impairment (MCI). Patients and normals will be drawn from the Mayo Alzheimer's Disease patient registry (AGO6786) and Alzheimer's Disease Research Center (AG16574). We will employ five different MR measures: medial temporal lobe structural measures; 1H MRS; leukoaraiosis volume; whole brain and ventricular volume, and lobar volume measures. In addition to established imaging technology, we will use a very promising new method of image registration and subtraction, and a new method for non-linear deformation (warping) of structural MRI. The grant contains three specific aims. Aim 1- to test the hypothesis that MRI/MRS measurements at baseline can predict the development of AD in normals and MCIs. Specific Aim 2 - to test the hypothesis that rates of change in MRI/MRS measurements derived from serial imaging studies are valid biomarkers of AD disease progression in normals and MCIs. Specific Aim 3 - to test the hypothesis that MRI/MRS measures are associated with change in performance on formal tests of cognition in normals, MCIs, and subjects with AD; where the dependent variables are continuous measures of cognitive performance rather than clinical group transitions. Currently no absolute diagnostic marker exists for AD. In anticipation of the coming era of therapeutic prevention and treatment for AD, better methods are needed to identify the risk of developing the disease and to track progression of the disease. Results from this project will provide new information that address an area identified as high priority for research by both the National Institute on Aging and the FDA.